Research On Bio-electronic Integrated Smart Wound Dressing Systems

The repair and regeneration of the skin is a major problem in clinic.Infection is the most common complication of wound repair and an important reason to delay the wound repair pricess,leading to amputation and death.Antibacterial wound dressings are effective means to treat infection in clinic.However,the existing antibacterial wound dressings are not able to achieve the on-demand controllable release of antibacterial agents,resulting in the abuse of antibacterial agents and thus causing side effects.In addition,the timely detection of infection is of great significance in guiding the use of antibacterial agents and accelerating the wound healing process.However,the existing wound dressings do not have the functions of information acquisition;Moreover,the coverage of dressings on the wound site often causes the“black box”state of the wound repair process,which may make microbial infection not be found in time,and thus delay the optimal time for treatment.Therefore,there is an urgent need to develope novel types of smart wound dressings that can break the"black box"state of traditional wound care,realize the intelligent warning and on-demand treatment of infection.Based on the above issues,this thesis first constructed a UV-responsive antibacterial hydrogel dressing to achieve the responsive release of antibiotics,reduce the side effects and bacterial resistance.In brief,levofloxacin was conjugated onto polyethylene glycol by an adjacent nitro-benzyl derivative to obtain the polyprodrug that can be cleaved under UV irradiaton at 365nm.Then,the polyprodrug was physically loaded into poly（vinyl alcohol）/sodium alginate hydrogel to obtain the UV-responsive antibacterial hydrogel dressing and achieve the controllable release of antibiotics under UV light,which may solve the problems of uncontrolled release of antibacterial agent and side effects in traditional wound dressing.To further achieve the monitoring and intelligent warning of wound infection,we fabricated a double-layered smart antibacterial hydrogel/flexible electronic integrated system by combing the flexible electronic sensing technology.The upper layer was a flexible electronic device layer,in which a temperature sensor and LED ultraviolet point light source were integrated,and an APP in smart phone was also equipped to receive the temperature data in real-time and control the light on/off of the LEDs.The lower layer was an UV-responsive antibacterial hydrogel dressing.Differing from the previous work,in this hydrogle,gentamicin was covalently modified onto an azide-terminated polyethylene glycol by an o-nitrobenzyl derivative to prepare a UV-cleavable polyprodrug,and then the polyprodrug was chemically copolymerized into the polyethylene glycol hydrogel to achieve the“0/1”on demand release of antibioticsas under ultraviolet light.The integrated system had high-sensitivity,stability,biocompatibility as well as long-term reliability in humid environments.By creating the animal wound infection model and implanting the integrated system as a wound dressing to monitor wound temperature in real time,the integrated system can realize the intelligent warning of wound infection and guide the in-situ on-demand controable release of antibiotics from the hydrogel layer under UV-LED light and thus treate infection effectively.To improve the problems of poor mechanical compatibility and biocompatibility between traditional flexible electronic devices and biological tissues,we constructed a conductive hydrogels-based smart dressing by combining the advantages of hydrogels and conductive materials.In brief,by introducting to PVP/TA/Fe³⁺cross-linking network into polyisopropylacrylamide（PNIPAM）hydrogel,a temperature-sensitive P（NIPAM-AM）/PVP/TA/Fe³⁺hydrogel-based bioelectronics device with a volume phase transition temperature of 37.5-38.5°C was obtained,in which acrylamide was copolymerizated with NIPAM to increase the volume phase transition temperature of PNIPAM hydrogel.As a temperature sensor,the hydrogel could realize the early warning of overheating of the wound by changing the electrical signal based on temperature.In addition,researches showed that the hydrogel had excellent strain-responsive capabilities and could be used as a flexible strain sensor to monitor large-scale human movements（such as fingers,wrists,etc.）and weak human activities（such as pulse,swallowing,etc.）.